Polyazamacrocyclic compounds are of considerable interest in the field of coordination chemistry. These ligands in particular form stable complexes with transition elements and heavy metals (Bradshaw J. S, Krakowiak K. E, Izatt R. M, Aza-crown Macrocycles in The Chemistry of Heterocyclic Compounds; edited by Taylor E. C, John Wiley and Son Inc.: New York, 1993, pp. 1-885; Izatt R. M, Pawlak K, Bradshaw J. S, Bruening R. L, Chem. Rev., 1995, 95, 2529-2586). The dimensions of the macrocyclic cavity, the shape and the rigidity of the ring, the size of the chelated ring, and the number and the nature of the substituents carried by the nitrogen atoms are all factors which influence the affinity of the ligand with respect to a given metal ion and thus the selectivity with respect to other elements. These properties have made possible the use of these compounds in fields as varied as the selective coordination of atmospheric dioxygen (Cabani S. React. and Funct. Polym., 1996, 167-182; Machida R, Kimura E, Kodama M, Inorg. Chem., 1983, 22, 2055-2061), medical imaging (Alexander V, Chem. Rev., 1995, 95, 273-342) or the extraction of metal elements (Guilard, R, Chollet H, Guiberteau P, Cocolios P, WO 96/11189, published on Apr. 18, 1996, FR 2725382 published on Apr. 12, 1996; Izatt R. M, Bruening R. L, Borup M. B, Water Sci. Technol., 1991, 23, 301-308).
In the field of the extraction of heavy metals and of the purification of effluents, the major disadvantage of these nitrogenous macrocycles is their solubility both in water and organic solvents, which results in a loss of the ligand when it is used in a liquidxe2x80x94liquid extraction process. On the other hand, the immobilization of the ligand on a solid support makes possible the development of a solid-liquid extraction process which exhibits numerous advantages, such as a reduced cost (no loss of the ligand), the noncontamination of the solvents to be purified, and easy use and regeneration of the columns. In the context of gas separation or purification, it is known, for example, that tetraazamacrocyclic cobalt complexes exhibit a high affinity with respect to dioxygen. However, the superoxide oxygen-comprising species formed can change in the direction of species of xcexc-peroxo type which have a limited lifetime in solution, where they undergo irreversible decomposition reactions (Martell A. E, Basak A. K, Raleigh C. J, Pure Appl. Chem., 1988, 60, 1325-1329). The attachment of the active complex to a solid matrix results in the superoxide species, which promotes the reversibility of the reaction and limits the decomposition of the oxygen-comprising species. Thus, absorption/desorption cycles might be carried out by lowering the pressure and/or raising the temperature.
Some industrial sectors, for example electronics, use liquids or gases of very high purity and environmental standards are becoming increasingly strict. Consequently, the development of processes which make it possible to remove trace amounts constitutes a priority. To this end, numerous modified polymers possessing selective chelating properties have been developed. Silica gels are among the most widely used supports (Biernat J. F, Konieczka P, Tarbet B. J, Bradshaw J. S, Izatt R. M, Sep. Purif. Methods, 1994, 23, 77-348). This is because they exhibit numerous advantages with respect to organic polymers: they are inexpensive, mechanically and thermally stable, inert with respect to numerous chemicals and insoluble in most organic solvents and can be easily modified.
Various silica gels modified by polyazamacrocyclic ligands have already been synthesized (Gros C, Rabiet F, Denat F, Brandes S, Chollet H, Guilard R, J. Chem. Soc. Dalton Trans., 1996, 1209-1214; Subba Rao Y. V, De Vos D. E, Bein T, Jacobs P. A, Chem. Commun., 1997, 355-356; Bagnoud M. A, Haerdi W, Veuthey J. L, Chromatographia, 1990, 29, 495-499; Izatt R. M, Bruenig R. L, Tarbet B. J, Griffin L. D, Bruening M. L, Krakowiak K. E, Bradshaw J. S, Pure Appl. Chem., 1990, 62, 1115-1118; Dudler V, Lindoy L. F, Sallin D, Schlaepfer C. W, Aust. J Chem., 1987, 40, 1557-1563). The most commonly used synthetic route (route A) is represented diagrammatically as follows:
During a first stage, a spacer arm carrying an electrophilic ending is attached to the silica gel by reaction of the appropriate silylated reactant (generally an alkoxysilane) with the silanol sites. Various assembling groups, such as those which appear hereinabove, can thus be used. The unreacted silanol sites can optionally be protected by the action of trimethylchlorosilane, in order to increase the selectivity of the gel or the hydrophobic nature of the latter. The desired macrocycle is subsequently condensed onto the modified silica gel. In a final stage, the grafted macrocycle can be N-substituted by the action of an appropriate electrophilic reactant. The amount of macrocycle grafted according to this synthetic scheme is approximately 0.35-0.40 mmol/g of material.
Another possible route of access to modified silica gels of this type (route B) consists, in a first stage, in functionalizing the macrocycle with the spacer arm, the grafting onto the silica subsequently taking place in a final stage: Bradshaw et al. (Izatt R. M, Bruening R. L, Tarbet B. J, Griffin L. D, Bruening M. L, Krakowiak K. E, Bradshaw J. S, Pure Appl. Chem., 1990, 62, 1115-1118, Bradshaw J. S, Krakowiak K. E, Tarbet B. J, Bruening R. L, Griffin L. D, Cash D. E, Rasmussen T. D, Izatt R. M, Solv. Extract Ion Exch., 1989, 7, 855-864) have thus developed a method which makes it possible to graft pentaazamacrocycles and various mixed (oxygen-nitrogen) macrocycles onto a silica gel, represented diagrammatically as follows:
In a first stage, a substituent carrying a terminal ethylene unit is attached to the desired macrocycle. The compound is subsequently hydrosilylated and the product thus obtained is condensed onto the silica gel.
However, the first synthetic route (A) exhibits two major disadvantages:
Only 30 to 50% of the spacer arms grafted in the first stage react with the macrocycle. The amount of grafted macrocycles is thus greatly reduced thereby and the residual presence of the unreacted functional groups can prove to be harmful during the implementation of a process using these materials for a given application.
The N-functionalization of the grafted tetraazamacrocycle, the final stage in the synthesis, is not quantitative as only one to two secondary amine functional groups of the three available react with the electrophilic reactant. In addition, some macrocycles may be bonded by two nitrogen atoms to the silica gel. This heterogeneity is harmful to the effectiveness and to the selectivity of the modified silica gel.
The synthetic route (B), while it makes it possible to control the substitution of the grafted ligand, is problematic to carry out, however, and it requires the use of expensive catalysts, such as hexachloroplatinic acid. The subject-matter of the present invention provides an unexpected solution to the problems set out hereinabove.
A subject-matter of the invention is a process for the preparation of a polyazacycloalkane, immobilized on a silica gel, from a polyazacycloalkane of formula (A): 
in which
R1 and R2, which are identical or different, each represent, independently of one another, a hydrogen atom, a linear or branched alkyl radical comprising from 1 to 15 carbon atoms,
W1, W2 and W3, which are identical or different, represent, independently of one another, a divalent radical chosen from those represented by the general formula (B):
xe2x80x94[(CT1T2)nxe2x80x94[N(R3)]pxe2x80x94(CT3T4)m]1xe2x80x94xe2x80x83xe2x80x83(B)
in which
p represents an integer equal to 1 or equal to 0,
l represents an integer equal to 1 or to 2,
n and m, which are identical or different, each represent, independently of one another, an integer less than or equal to 3 and greater than or equal to 1,
T1, T2, T3 and T4, which are identical or different, either each represent, independently of one another, a hydrogen atom, a linear or branched alkyl radical comprising from 1 to 15 carbon atoms or else CT1T2 and/or CT3T4 represent the divalent group xe2x80x94(Cxe2x95x90O)xe2x80x94,
R3 represents, independently of R1 or R2, a hydrogen atom, a liner or branched alkyl radical comprising from 1 to 15 carbon atoms,
xe2x80x83which comprises:
a) the reaction of the compound of formula (A) with a compound of formula (C)
Zxe2x80x94R4xe2x80x94Si(X1)(X2)(X3)xe2x80x83xe2x80x83(C)
xe2x80x83in which:
X1, X2 and X3, which are identical or different, each represent, independently of one another, a hydrogen atom, a halogen atom or an OR5 radical, in which R5 represents a hydrogen atom or an alkyl radical comprising from 1 to 4 carbon atoms,
R4 represents a divalent radical derived from a saturated or unsaturated aliphatic hydrocarbonaceous chain comprising from 1 to 10 carbon atoms, in which chain are optionally inserted one or more structural links chosen from the arylene group or the xe2x80x94Oxe2x80x94, xe2x80x94Sxe2x80x94, xe2x80x94Oxe2x80x94C(xe2x95x90O)xe2x80x94, xe2x80x94N(R6)xe2x80x94C(xe2x95x90O)xe2x80x94 or xe2x80x94N(R6)xe2x80x94 fragments, in which fragments R6 represents a hydrogen atom, an aliphatic hydrocarbonaceous radical comprising from 1 to 6 carbon atoms, a benzyl radical or a phenethyl radical, the said chain being unsubstituted or substituted by one or more radicals chosen from halogen atoms, the hydroxyl group, alkyl radicals comprising from 1 to 4 carbon atoms or the benzyl or phenethyl radicals, and
Z represents a functional group capable of reacting with the secondary amine functional group, xe2x95x90Nxe2x80x94H, to form an Nxe2x80x94C covalent bond, to form a compound of formula (D), 
xe2x80x83in which Rxe2x80x24 represents either R4 as defined above, or R4 substituted by a radical originating from the reaction of Z with the secondary amine group xe2x95x90Nxe2x80x94H,
b) the condensation of said compound of formula (D) with silanol sites of a silica gel, to form the immobilized polyazacycloalkane of formula (E): 
xe2x80x83in which:
Xxe2x80x22 represents X2 as defined above or O-(silica gel), and
Xxe2x80x23 represents X3 as defined above or O-(silica gel);
c) and the protection, if desired, of all or a portion of the free unreacted silanol sites with Zxe2x80x2, a protective group for the hydroxyl functional group.
The term xe2x80x9cpolyazacycloalkane of formula (A)xe2x80x9d denotes non-immobilized polyazacycloalkanes known to a person skilled in the art at the date of filing of the present patent application.
When the compound of formula (A) comprises three cyclic nitrogen atoms, it is in particular 1,4,7-triazacyclononane, 1,4,7-triazacyclodecane or 1,4,8-triazacyclododecane.
When the compound of formula (A) comprises four cyclic nitrogen atoms, it is in particular 1,4,7,10-tetraazacyclododecane (cyclene), 1,4,7,10-tetraaza-cyclotridecane, 1,4,7,11-tetraazacyclotetradecane, 1,4,8,11-tetraazacyclotetradecane (cyclam), 1,4,8,12-tetraazacyclopentadecane, 1,5,9,13-tetraazacyclohexa-decane or 1,5,10,14-tetraazacyclooctadecane.
When the compound of formula (A) comprises five cyclic nitrogen atoms, it is in particular 1,4,7,10,13-pentaazacyclopentadecane, 1,4,7,11,15-pentaazacyclo-octadecane or 1,5,9,13,17-pentaazacyclooctadecane.
When the compound of formula (A) comprises six cyclic nitrogen atoms, it is in particular 1,4,7,10,13,16-hexaazacyclooctadecane or 1,5,9,13,17,20-hexaazacyclotetracosane.
The compound of formula (A) can be unsubstituted or substituted; when it is substituted, the substituents are chosen from those which do not react under the operating conditions with the compound of formula (B); examples of substituted polyazacycloalkanes are those substituted by alkyl radicals comprising from 1 to 15 carbon atoms or the benzyl, picolyl or phenethyl radicals, such as 6-dodecyl-1,4,8,11-tetraazacyclotetradecane, 3-dodecyl-1,5,9,13-tetraazacyclohexadecane, 3-dodecyl-1,5,10,14-tetraazacyclooctadecane, 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradecane, 1,4,7,10,13-pentaethyl-1,4,7,10,13,16-hexaazacyclooctadecane, 1,7,10-tetraethyl-1,4,7,10,13-pentaazacyclopentadecane, 1-methyl-1,4,8,11-tetraazacyclotetradecane, 1-benzyl-1,4,8,11-tetraazacyclotetradecane, 1-[(2-pyridyl)-methyl]-1,4,8,11-tetraazacyclotetradecane, 1-[(3-pyridyl)methyl]-1,4,8,11-tetraazacyclotetradecane or 1,4-dibenzyl-1,4,8,11-tetraazacyclotetradecane.
The term xe2x80x9cfunctional group capable of reacting with a secondary aminexe2x80x9d denotes in particular those which react according to a nucleophilic substitution mechanism, such as, for example, the halogen radicals and particularly the iodo radical, or those which react according to an electrophilic addition mechanism, such as, for example, the epoxy functional group, which results in an Nxe2x80x94CH2xe2x80x94CH(OH) fragment; it can also be a free, salified or esterified carboxyl functional group or a CH2xe2x95x90CHxe2x80x94 group, which results in an Nxe2x80x94CH2xe2x80x94CH2xe2x80x94 fragment via a reaction of xe2x80x9cMichaelxe2x80x9d type according to a nucleophilic addition mechanism. These examples do not have a limiting nature and it is obvious that any functional group known to a person skilled in the art at the date of filing of the present patent application as being capable of reacting with a secondary amine functional group to form an Nxe2x80x94CH covalent bond forms an integral part of the present description of the invention.
The term xe2x80x9cprotective group for the hydroxyl functional groupxe2x80x9d denotes, for Zxe2x80x2, any group resulting from an etherification or esterification reaction with Sixe2x80x94OH; mention may in particular be made, as example of Zxe2x80x2 group, of the trialkylsilyl radical in which each of the alkyl radicals comprises, independently of one another, from 1 to 4 carbon atoms.
According to a first specific aspect of the process as defined above, the latter is carried out with a compound of formula (C1):
Zxe2x80x3xe2x80x94(CH2)oxe2x80x94(Q)qxe2x80x94(CH2)rxe2x80x94(Ar)sxe2x80x94(CH2)txe2x80x94(U)uxe2x80x94(CH2)vxe2x80x94Si(X1)(Xs)(X3)xe2x80x83xe2x80x83(C1)
corresponding to the formula (C) in which Zxe2x80x94R4 represents the radical:
Zxe2x80x3xe2x80x94(CH2)oxe2x80x94(Q)qxe2x80x94(CH2)rxe2x80x94(Ar)sxe2x80x94(CH2)txe2x80x94(U)uxe2x80x94(CH2)vxe2x80x94
in which:
Zxe2x80x3 represents either a halo radical or an R7Oxe2x80x94C(xe2x95x90O)xe2x80x94 group, in which R7 represents a hydrogen atom, a sodium atom, a potassium atom or a radical chosen from alkyl radicals comprising from 1 to 4 carbon atoms or the tosyl, mesyl or trifluoromethylsulfonyl radicals, or an oxiran-2-yl group or an ethenyl group,
o, r, t and v, which are identical or different, represent, independently of one another, an integer greater than or equal to 0 and less than or equal to 6,
Q and U, which are identical or different, represent, independently of one another, an oxygen atom, a sulfur atom or one of the xe2x80x94Oxe2x80x94COxe2x80x94, xe2x80x94COxe2x80x94Oxe2x80x94, xe2x80x94NHxe2x80x94COxe2x80x94, xe2x80x94COxe2x80x94NHxe2x80x94 or xe2x80x94NHxe2x80x94 groups,
q, s and u, which are identical or different, represent, independently of one another, an integer greater than or equal to 0 and less than or equal to 1,
Ar represents an arylene radical and in particular a phenylene radical,
it being understood that:
when q is equal to 1, o is other than 0,
when q is equal to 1 and when u is equal to 0, the sum r+s+t+v is other than 0,
when u is equal to 1, v is other than 0,
when u is equal to 1 and when q is equal to 0, the sum o+r+s+t is other than 0,
when s is equal to 0 and when q and u are each equal to 1, the sum r+t is other than 0, and
the sum o+r+t+v is less than or equal to 12.
The process which is the subject-matter of the present invention is carried out in particular with a compound of formula (C2), corresponding to the formula (C1) as defined above in which:
Zxe2x80x3 represents a bromo radical, an iodo radical or an oxiran-2-yl radical,
(X1), (X2) and (X3) each represent an ethoxy radical or a methoxy radical,
the sum of o+r+t+v is less than or equal to 6 and
the sum of q+u is less than or equal to 1.
The process is carried out in particular with the following products:
(triethoxy)(3-iodopropyl)silane,
2-[[[3-(triethoxysilyl)propyl]oxy]methyl]-oxirane and
N-[[4-(bromomethyl)phenyl]methyl]-N-[3-(triethoxysilyl)propyllamine.
The compounds of formulae (C) and (C1) are obtained from commercially available products by methods known to a person skilled in the art.
According to another specific aspect of the process as defined above, the latter is carried out from a compound of formula (A1), corresponding to the formula (A) as defined above in which:
W1, W2 and W3, which are identical or different, represent, independently of one another, a divalent radical chosen from those represented by the general formula (B1):
xe2x80x94(CH2)nxe2x80x94(NH)pxe2x80x94(CH2)mxe2x80x94xe2x80x83xe2x80x83(B1)
xe2x80x83in which:
n and m are, independently of one another, equal to 2 or to 3 and p is equal to 0 or to 1.
The process is carried out in particular from a compound of formula (A2), corresponding to the formula (A1) in which the R1 and R2 radicals each represent a hydrogen atom, and more particularly from cyclam, a compound of formula (A2) as defined above in which W1 represents the divalent radical xe2x80x94(CH2)3xe2x80x94NHxe2x80x94(CH2)2xe2x80x94, W2 represents the divalent radical xe2x80x94(CH2)2xe2x80x94 and W3 represents the divalent radical xe2x80x94(CH2)3xe2x80x94, or from cyclene, a compound of formula (A2) in which W1 represents the divalent radical xe2x80x94(CH2)2xe2x80x94NHxe2x80x94(CH2)2xe2x80x94 and W2 and W3 each represent the divalent radical xe2x80x94(CH2)2xe2x80x94.
In an alternative form of the process which is a subject-matter of the present invention, the compound of formula (D1), corresponding to the formula (D) as defined above in which at least one of the R1, R2 or R3 radicals represents a hydrogen atom, is functionalized beforehand on one or more of its cyclic nitrogens to form a compound of formula (Dxe2x80x2) 
in which:
Rxe2x80x24, X1, X2 and X3 are as defined above,
Rxe2x80x21 and Rxe2x80x22, which are identical or different, represent, independently of one another, a hydrogen atom, a linear or branched alkyl radical comprising from 1 to 15 carbon atoms, a [hetero(aryl)]alkyl radical comprising from 7 to 12 carbon atoms or a xe2x80x94(CH2)wxe2x80x94C(xe2x95x90O)xe2x80x94V radical in which V represents one of the OH, NH2 or OR8 radicals, in which R8 represents an alkyl radical comprising from 1 to 4 carbon atoms, and w represents an integer greater than or equal to 1 and less than or equal to 6;
Wxe2x80x21, Wxe2x80x22 and Wxe2x80x23, which are identical or different, represent, independently of one another, a divalent radical chosen from those represented by the general formula (Bxe2x80x2):
xe2x80x94[(CT1T2)nxe2x80x94[N(Rxe2x80x23)]pxe2x80x94(CT3T4)m]lxe2x80x94xe2x80x83xe2x80x83(Bxe2x80x2)
xe2x80x83in which:
p, l, n, m, T1, T2, T3 and T4 have the same meanings as those defined above for the formula (B),
Rxe2x80x23 represents, independently of Rxe2x80x21 or Rxe2x80x22, a hydrogen atom, a linear or branched alkyl radical comprising from 1 to 15 carbon atoms, or a
xe2x80x94(CH2)wxe2x80x94C(xe2x95x90O)xe2x80x94V radical in which V represents one of the OH, NH2 or OR8 radicals, in which R8 represents an alkyl radical comprising from 1 to 4 carbon atoms, and w represents an integer greater than or equal to 1 and less than or equal to 6,
it being understood that at least one of the Rxe2x80x21, Rxe2x80x22 or Rxe2x80x23 radicals represents a xe2x80x94(CH2)wxe2x80x94C(xe2x95x90O)xe2x80x94V radical,
before being grafted onto the silanol sites of the silica gel to form an immobilized and functionalized macrocycle of formula (Exe2x80x2), corresponding to the formula (E) in which R1, R2 and R3 represent Rxe2x80x21, Rxe2x80x22 and Rxe2x80x23 respectively.
When this alternative form of the process which is the subject-matter of the present invention is carried out, it is preferable to prepare a compound of formula (Dxe2x80x21), corresponding to the formula (Dxe2x80x2) as defined above in which none of the Rxe2x80x21, Rxe2x80x22 or Rxe2x80x23 radicals represents a hydrogen atom.
This alternative variant of the process is carried out in a particularly appropriate way from the compound of formula (A2) as defined above, which results in the compound of formula (D2), corresponding to the formula (D) in which W1, W2, W3, R1 and R2 are as defined in the formula (A2), and then in the compound of formula (Dxe2x80x22), corresponding to the formula (Dxe2x80x2) as defined above in which Rxe2x80x21, Rxe2x80x22 and Rxe2x80x23 each represent a xe2x80x94(CH2)wxe2x80x2xe2x80x94C(xe2x95x90O)xe2x80x94ORxe2x80x28 radical, in which wxe2x80x2 is equal to 1, 2 or 3 and Rxe2x80x28 represents a hydrogen atom, a methyl radical or an ethyl radical.
The reactions for functionalizing the NH group are known to a person skilled in the art; one of them is disclosed in the international patent application published under No. WO96/11189 on Apr. 18, 1996.
Another subject-matter of the invention is the compounds of formulae (D) and (Dxe2x80x2) as defined above, in particular the compounds of formulae (D1), (D2), (Dxe2x80x21) and (Dxe2x80x22) as defined above, and more particularly the following products:
1-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclododecane,
1-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclotridecane,
1-[3-(triethoxysilyl)propyl]-1,4,8,11-tetraazacyclotetradecane,
1-[3-(triethoxysilyl)propyl]-1,4,8,12-tetraazacyclopentadecane,
1-[3-(triethoxysilyl)propyl]-1,5,9,13-tetraazacyclohexadecane,
1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,7,10-tetraazacyclododecane,
1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,7,10-tetraazacyclotridecane,
1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,8,11-tetraazacyclotetradecane,
1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,4,8,12-tetraazacyclopentadecane,
1-[2-hydroxy-3-[[3-(triethoxysilyl)propyl]oxy]-propyl]-1,5,9,13-tetraazacyclohexadecane,
1-[[4-[[[-3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,7,10-tetraazacyclododecane,
1-[[4-[[[-3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,7,10-tetraazacyclotridecane,
1-[[4-[[[-3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,8,11-tetraazacyclotetradecane,
1-[[4-[[[-3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,4,8,12-tetraazacyclopentadecane,
1-[[4-[[[-3-(triethoxysilyl)propyl]amino]-methyl]phenyl]methyl]-1,5,9,13-tetraazacyclohexadecane,
ethyl 10-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclododecane-1,4,7-tripropanoate,
ethyl 10-[3-(triethoxysilyl)propyl]-1,4,7,10-tetraazacyclotridecane-1,4,7-tripropanoate,
ethyl 11-[3-(triethoxysilyl)propyl]-1,4,8,11-tetraazacyclotetradecane-1,4,8-tripropanoate,
ethyl 12-[3-(triethoxysilyl)propyl]-1,4,8,12-tetraazacyclopentadecane-1,4,8-tripropanoate,
ethyl 13-[3-(triethoxysilyl)propyl]-1,5,9,13-tetraazacyclohexadecane-1,5,9-tripropanoate,
ethyl 10-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,7,10-tetraazacyclododecane-1,4,7-tripropanoate,
ethyl 10-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,7,10-tetraazacyclotridecane-1,4,7-tripropanoate,
ethyl 11-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,8,11-tetraazacyclotetradecane-1,4,8-tripropanoate,
ethyl 12-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,4,8,12-tetraazacyclopentadecane-1,4,8-tripropanoate,
ethyl 13-[2-hydroxy-3-[[3-(triethoxysilyl)-propyl]oxy]propyl]-1,5,9,13-tetraazacyclohexadecane-1,5,9-tripropanoate,
ethyl 10-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,7,10-tetraazacyclododecane-1,4,7-tripropanoate,
ethyl 10-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,7,10-tetraazacyclotridecane-1,4,7-tripropanoate,
ethyl 11-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,8,11-tetraazacyclotetradecane-1,4,8-tripropanoate,
ethyl 12-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,4,8,12-tetraazacyclopentadecane-1,4,8-tripropanoate, and
ethyl 13-[[4-[[[3-(triethoxysilyl)propyl]-amino]methyl]phenyl]methyl]-1,5,9,13-tetraazacyclohexadecane-1,5,9-tripropanoate.
An example of the implementation of the process according to the invention is illustrated by the following schemes:
Iodopropyltriethoxysilane is synthesized simply by the action of NaI on commercial chloropropyltriethoxysilane. The iodopropyltriethoxysilane, in solution in acetonitrile, is then added dropwise to a solution of cyclam in acetonitrile at reflux in the presence of Na2CO3. The reaction mixture is maintained at reflux for 24 h, the solvent is subsequently evaporated and pentane is added to the residue. The excess insoluble cyclam is filtered off, the filtrate is concentrated and compound 1 is obtained without subsequent purification with a yield of 50%. The grafting of 1 onto the silica gel is carried out at reflux of the xylene for 4 days. The amount of grafted macrocycles is then 0.8 mmol/g of modified silica gel.
Compound 1 can be functionalized and then subsequently grafted according to the scheme:
Compound 1 is stirred for 4 days at room temperature in ethyl acrylate. After evaporating the ethyl acrylate and washing several times with pentane, the product 2 is obtained quantitatively. The grafting of 2 onto the silica gel is subsequently carried out as described above.
If this methodology is compared with that which proceeds by grafting the spacer group onto the silica gel and then by attaching the desired ligand to this arm, this novel process makes it possible to double the amount of tetraazamacrocycles grafted at the surface of the silica gel. The number of xe2x80x9cactive sitesxe2x80x9d per unit of surface area is thus significantly increased, resulting in a considerable improvement in the effectiveness of the material. The second advantage, which is even more important, is to be able to completely control the nature of the ligand attached, since it is synthesized, isolated and characterized before grafting.
This novel method for the synthesis of ligands carrying the spacer arm does not require special experimental conditions and results, with suitable yields, in the expected compounds without subsequent purification. In addition, this synthesis is carried out in a single stage and not two as in the methodology involving the hydrosilylation of the terminal alkene. Finally, the N-substitution of these novel ligands is quantitative and makes possible the grafting of completely N-substituted macrocycles.
This method applies not only to the compound of formula (A) as defined above but also to linear polyamines. Various spacer arms (comprising aromatic units or ester or amide functional groups) can be used. The electrophilic reactant used during the N-functionalization can also vary, making possible access to a large range of silica gels exhibiting an optimum effectiveness and an optimum selectivity.
The macrocycles grafted onto a silica gel by the process which is the subject-matter of the present invention are used for removing metal cations from a liquid, in particular removing cations chosen from U, Pu, Am, Ce, Eu, Al, Gd, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ag, Cd, Sn, Au, Hg or Pb.
The macrocycles grafted onto a silica gel by the process which is the subject-matter of the present invention are also used to prepare complexes with transition metals, said transition metal complexes being used for the separation and the removal of oxygen from a gas mixture, such as air, comprising it.